Pharmacogenomic Discovery to Function and Mechanism: Breast Cancer as a Case Study

Abstract

Biomedical research is undergoing rapid change, with the development of a series of analytical omics techniques that are capable of generating Biomedical Big Data. These developments provide an unprecedented opportunity to gain novel insight into disease pathophysiology and mechanisms of drug action and response—but they also present significant challenges. Pharmacogenomics is a discipline within Clinical Pharmacology that has been at the forefront in defining, taking advantage of, and dealing with the opportunities and challenges of this aspect of the Post-Genome Project world. This overview will describe the evolution of germline pharmacogenomic research strategies as we have moved from an era of candidate genes to agnostic genome-wide association studies (GWAS) coupled with the functional and mechanistic pursuit of GWAS signals. Germline pharmacogenomic studies of breast cancer endocrine therapy will be used to illustrate research strategies that are being applied broadly to omics studies of drug response phenotypes.